This study investigated the potential contribution of nitric oxide (NOx) production to enhanced fetal hemoglobin (HbF) synthesis in patients with diabetes. Glycated hemoglobin (HbA1c), HbF, high sensitivity C-reactive protein (hsCRP), plasma glucose levels, and serum NOx concentrations were measured in 350 diabetics and 125 healthy subjects. There were no significant correlations between HbF and HbA1c levels, nor between HbF and plasma glucose levels. However, serum NOx concentrations in patients with HbF >1.0% (76.2 ± 32.4 μmol/L) were significantly higher than those with HbF ≤ 1.0% (47.3 ± 29.8 μmol/L, p <0.05). Inversely, patients with moderately increased serum NOx levels >98.1 μmol/L (75th percentile of patients) exhibited significantly higher HbF levels than those with decreased serum NOx levels <34.2 μmol/L (25th percentile of patients) (1.16 ± 0.41 vs. 0.62 ± 0.28%, p <0.05). After excluding the subjects with high NOx levels, elevated HbF concentrations returned to a level not significantly different from the control value. Serum NOx concentrations were significantly correlated with HbF (r = 0.32, p <0.05) and hsCRP levels (r = 0.35, p <0.05) in diabetic patients. In conclusion, long-term glycemic control does not contribute to fetal-type erythropoiesis, but increased NOx production seems to play an important role in the enhanced HbF synthesis of diabetics.